PROJECT SUMMARY/ABSTRACT The proposed project, ?Identifying neurobiological predictors of alcohol use onset during adolescence?, responds to the need for a better understanding of the characteristics present prior to initiation of alcohol use that may represent risk factors for use onset during adolescence. Early initiation of alcohol use is considered one of the most important risk factors in the later development of alcohol and substance use disorders, but it is not yet well understood when initiation of use is driving neurobiological changes that account for this increased vulnerability, and when initiation is largely a proxy for pre-existing traits and neurobiological patterns, which may actually be responsible for the risk. The present prospective study therefore aims to identify those neurobiological and behavioral markers that exist prior to the initiation of alcohol use and may confer risk for earlier use onset. Specifically, the study will rely on analysis of functional connectivity data from a hippocampus-mediated spatial memory task and a frontally-mediated response inhibition task, in order to test the importance of hippocampus-PFC integration in informing adaptive decision-making and reducing risky behaviors. Adolescents are being enrolled into the study prior to the initiation of alcohol or other drug use at 13-14 years old for a baseline scanning visit, and are being followed for two years via annual visits and quarterly phone interviews to assess initiation of alcohol and substance use and other risky behaviors. Baseline scanning includes acquisition of structural magnetic resonance imaging (MRI), task functional magnetic resonance imaging (fMRI) during response inhibition and spatial memory tasks, and resting state perfusion (PCASL). Magnetic resonance measures are being integrated with measures from clinical assessments and an extensive neuropsychological battery, designed to detect and further characterize patterns that may be predictive of initiation and other risky alcohol and drug use in adolescence. Together these data will provide a foundation for informing neurobehavioral targets and strategies for prevention and intervention efforts in maladaptive alcohol and substance use.